Abstract

Hepatitis A virus cellular receptor 1 (HAVCR1), which is also known as T-cell immunoglobulin and mucin domain 1 (TIM-1) is a TIM gene family member. In this study, we aimed to characterize the expression profile of HAVCR1 in GC, its prognostic value and the potential epigenetic mechanism leading to its dysregulation. Bioinformatic analysis was performed by using genomic, clinicopathological and survival data in the human protein atlas (HPA) and the Cancer Genome Atlas (TCGA). Results showed that HAVCR1 was significantly upregulated at the mRNA and protein level in GC tissues compared to the adjacent normal tissues. In addition, HAVCR1 upregulation was an independent indicator of shorter OS (HR: 1.698, 95%CI: 1.221–2.361, p = 0.002), after adjustment of older age, differentiation status, pathological stages and the presence of residual tumor and was also an independent indicator of shorter RFS (HR: 2.577, 95%CI: 1.583–4.197, p<0.001), after adjustment of gender and histological grade. The methylation level of two CpG sites (cg11188031 and cg07320595) was negatively correlated with HAVCR1 expression. However, only high methylation level of cg07320595 was associated with significantly longer OS (p = 0.018) and RFS (p = 0.021). Based on these findings, we infer that HAVCR1 upregulation might serve as a valuable prognostic marker in terms of OS and RFS in GC patients. Cg07320595 might be a critical CpG site influencing HAVCR1 expression.

Highlights

  • Hepatitis A virus cellular receptor 1 (HAVCR1), known as T-cell immunoglobulin and mucin domain 1 (TIM-1) is a TIM gene family member [1]

  • Results showed that HAVCR1 expression varied significantly in different human tissues (Fig 1A and 1B)

  • Representative IHC image showed that HAVCR1 staining was low in glandular cells in normal stomach tissues (Fig 2B, left)

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Summary

Introduction

Hepatitis A virus cellular receptor 1 (HAVCR1), known as T-cell immunoglobulin and mucin domain 1 (TIM-1) is a TIM gene family member [1]. It is a class I integral membrane glycoprotein, which contains an N-terminal extracellular immunoglobulin (Ig)-like domain, an extended mucin-like domain, a single transmembrane domain, and a C-terminal short cytoplasmic tail, allowing accessibility to interactions with extracellular proteins [2]. HAVCR1 is preferentially expressed on Th2 cells, inducing T-cell activation and inhibiting the development of peripheral tolerance [6, 7]. This molecule is involved in the moderation of allergic response and asthma [5]. The cleaved ectodomain of HAVCR1 can be detected in the urine samples from RCC patients, making it a possible biomarker for early detection of RCC [10]

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